Electroencephalographic abnormalities in aseptic meningitis and noninfectious headache. A comparative study

BACKGROUND: The finding of abnormalities on electroencephalogram (EEG) during the course of aseptic meningitis is often considered to be indicative of parenchymal brain involvement, even in absence of clinical signs of encephalitis. OBJECTIVE: To investigate if patients with aseptic nonherpetic meningitis who have abnormal EEG recordings during the acute stage of the disease differ in clinical characteristics or cerebrospinal fluid findings from patients with aseptic meningitis and normal EEG recordings. METHODS: The EEG records of 82 patients with aseptic meningitis were reviewed. A comparative group consisted of 41 age-matched patients with severe headaches without evidence of meningeal inflammation. RESULTS: Significantly more patients with aseptic meningitis (28%) demonstrated abnormalities on EEG than controls (12%) (P =.048). Patients with aseptic meningitis and abnormal EEG findings (n = 23) did not differ in age, duration of symptoms, clinical course, cerebrospinal fluid cell count, or protein level from those with normal EEG findings (n = 59). However, all patients with aseptic meningitis who were confused (n = 5) also revealed EEG abnormalities (P<.00012). Patients with headache with normal EEG recordings did not differ from those with abnormal EEGs in age, sex, or duration of symptoms. Nevertheless, patients with common migraine (n = 9) showed abnormalities on EEG (P =.06) more frequently. CONCLUSIONS: The finding of an abnormal EEG in patients with aseptic meningitis, clear mental state and absence of focal neurological signs should not be used as proof of encephalitis. Because pathological examination is usually not performed, it remains unclear if EEG abnormalities in patients with aseptic meningitis indicate a silent parenchymal inflammation, or reflect an infectious encephalopathy.     

Subcutaneous sumatriptan induces changes in frequency pattern in cluster headache patients

OBJECTIVES: To document the relationship between the use of subcutaneous (SQ) sumatriptan (sum) and a change in frequency pattern of cluster headache (CH) in six patients. To discuss the clinical and pathophysiological implications of this observation in the context of available literature. BACKGROUND: Treatment with SQ sum may cause an increase in attack frequency of CH but data from literature are scant and controversial. METHODS: Six CH sum-na?ve patients (three episodic and three chronic according to the International Headache Society (IHS) criteria) are described. RESULTS: All six patients had very fast relief from pain and accompanying symptoms from the drug but they developed an increase in attack frequency soon after using SQ sum. In all patients, the CH returned to its usual frequency within a few days after SQ sum was withdrawn or replaced with other drugs. Five patients were not taking any prophylactic treatment and SQ sum was the only drug prescribed to treat their headache. CONCLUSIONS: Physicians should recognize the possibility that treatment of CH with SQ sum may be associated with an increased frequency of headache attacks.     

Intractable headache: aseptic meningitis and sphenoidal sinusitis

Sphenoid sinusitis, an uncommon cause of headache, is associated with significant morbidity. A 30-year-old man presented with a progressive intractable headache and aseptic meningitis. Failure to recognize sphenoid disease on brain CT delayed diagnosis; treatment with IV antibiotics resolved the disorder.     

Alteration in nature of cluster headache during subcutaneous administration of sumatriptan

OBJECTIVES: To document the relationship between the 5-HT receptor agonist sumatriptan and a change in the nature of cluster headache in four cases. To relate the findings to the literature on the use of sumatriptan in both cluster headache and migraine. BACKGROUND: Studies of the efficacy and adverse effects of long-term treatment with sumatriptan in cluster headache are limited and report conflicting findings. METHODS: Four cases are described. RESULTS: All four patients developed a marked increase in the frequency of attacks 3 to 4 weeks after initiating treatment with the drug for the first time. Three patients also developed a change in headache character, and 2 experienced prolongation of the cluster headache period. Withdrawal of the drug reduced the frequency of headaches and eliminated the newly developed type of headache. CONCLUSIONS: Determination of the effects of long-term use of sumatriptan will result in more precise guidelines for the frequency and duration of treatment with this otherwise extremely beneficial drug.     

Migraine-like headache in bacterial meningitis

The effect of sumatriptan has not been previously described in the treatment of the headache of meningitis, although this headache has similarities to migraine. This study presents the clinical features of two patients who had fulminant bacterial meningitis with migraine-like headache and who experienced no improvement in headache intensity after administration of sumatriptan 6 mg s.c. On these grounds the lack of response of this type of headache to sumatriptan is discussed.     

Treatment of cluster headache attacks with less than 6 mg subcutaneous sumatriptan

BACKGROUND: Subcutaneous (SQ) sumatriptan 6 mg is effective in the treatment of acute cluster headache attacks. However, patients sometimes benefit from a dose less than 6 mg. OBJECTIVE: Therefore, we designed a prospective open study to evaluate how many patients benefit from a dose less than 6 mg SQ sumatriptan. METHODS: We enrolled 81 consecutive patients with cluster headache and recorded their use of SQ sumatriptan and oxygen. Patients regularly using SQ sumatriptan 6 mg were advised to treat attacks with doses less than 6 mg and with oxygen. Efficacy and side effects of the different treatment options (6 mg, 3 mg, 2 mg, and oxygen) were evaluated. RESULTS: As a result, 74% of the patients using SQ sumatriptan 3 mg showed efficacy and 89% reported efficacy after 2 mg. Seventy-nine percent reported side effects after the use of SQ sumatriptan 6 mg (29% severe side effects). After the use of 2 mg SQ sumatriptan, only 50% of the patients reported side effects, none of these were classified as severe. Patients' preference was 41% for 6 mg sumatriptan, 28% for doses less than 6 mg, and 31% for oxygen. CONCLUSIONS: We conclude that sumatriptan in doses less than 6 mg can be effective in the acute treatment of cluster headache attacks. We suggest that patients should have experience in their individual efficacy of sumatriptan doses less than 6 mg.     

Ergotamine-induced headache can be sustained by sumatriptan daily intake

We describe the case report of a migraine sufferer who developed ergotamine-induced headache and subsequently replaced ergotamine with daily sumatriptan (100 mg p.o.). The features of the headache were unchanged except for the presence of superimposed migraine-like headaches that occurred every 24 h.     

Cluster headache attacks treated for up three months with subcutaneous sumatriptan (6 mg)

In the first three months of a 24-month open study to assess the safety and efficacy of subcutaneous sumatriptan 6 mg in the long-term acute treatment of cluster headache, 138 patients treated a maximum of two attacks daily each with a single 6 mg injection. A total of 6353 attacks were treated. Adverse events, reported in 28% of sumatriptan-treated attacks, were qualitatively similar to those seen in migraine long-term trials. Their incidence did not increase with frequent use of sumatriptan. There were no clinically significant treatment effects on vital signs, ECG recordings or laboratory parameters. Headache relief (a reduction from very severe, severe or moderate pain to mild or no pain) at 15 min was obtained for a median of 96% of attacks treated. There was no indication of tachyphylaxis, decrease in the speed of response, or increased frequency of attacks with long-term treatment. This study demonstrated that, in long-term use, subcutaneous sumatriptan 6 mg is a well-tolerated and effective acute treatment for cluster headache.     

Responsiveness of non-IHS migraine and tension-type headache to sumatriptan

In a long-term efficacy and satiety study, 424 patients were treated with sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to sumatriptan. An equivalent response to sumatriptan among three diagnostic groups of headache supports the concept of a common biologic mechanism involving 5HT₁ receptors that spans a range of clinical presentations.     

Dramatic headache relief after sumatriptan in a patient with a pituitary macroadenoma

We are reporting an interesting case of pituitary macroadenoma. The patient presented with sudden, bifrontal, pulsating headache; photophobia; and an abducens nerve palsy, due to extension of the tumor into the cavernous sinus region. The headache resolved completely after a subcutaneous injection of sumatriptan.     

Trimethoprim-sulfamethoxazole-induced aseptic meningitis: case report and literature review

Aseptic meningitis is a rare adverse drug reaction, reported with non-steroidal anti-inflammatory agents (NSAIDs) and with miscellaneous drugs such as trimethoprim-sulfamethoxazole (TMP-SMX). The most common clinical findings reported are fever, headache, stiffness and altered level of consciousness. We report a case of aseptic meningitis related to TMP-SMX ingestion that caused severe derangements of the patient's vital signs, requiring Intensive Care Unit admittance. The prompt diagnosis and discontinuation of the drug resulted in complete recovery. We examine the case according to the literature on this topic. We conclude that, since the signs and symptoms of this unusual drug reaction may mimic those of central nervous system infection, the clinician should consider this etiology when he is faced with a patient with suspected meningoencephalitis, especially if the latter has already been treated at home with unknown drugs. Further studies should investigate the pathogenetic mechanism of TMP-SMX-induced aseptic meningitis.     

Risk factors for headache recurrence after sumatriptan: a study in 366 migraine patients

Headache recurrence (HR) is the major limitation of sumatriptan in the acute treatment of migraine attacks. The risk of HR is mainly patient dependent. We analyzed, in 366 migraine patients, clinical differences between patients who always have HR and patients who never have HR. We found remarkably few differences. HR more frequently occurred in patients with more severe attacks and longer untreated attack duration; in patients who experienced a sensation of a subclinically ongoing attack, despite headache relief after sumatriptan; and in females, mainly with menstruation-related migraine, most probably due to the more severe and longer lasting attacks these patients suffer, rather than due to hormonal factors. The incidence of HR was, among other factors, not related to the (other) clinical effects of sumatriptan, the timing of administration within the attack, the duration of use of sumatriptan, pharmacokinetic factors, or whether patients were experiencing HR after use of ergot alkaloids.     

Chemical‐induced aseptic meningitis as a result of intrathecal hydromorphone therapy: Case report

Chemical meningitis, though rare, is a diagnosis of exclusion that must be considered in patients presenting with neurologic symptoms of undetermined cause. It is likely that any substance in contact with CSF can be the culprit.     

The 5-HT1-like agonist sumatriptan has a significant effect in chronic tension-type headache

Subcutaneous treatment of chronic tension-type headache with 2 mg and 4 mg sumatriptan, a selective 5-hydroxytryptamine1-like receptor agonist, was compared with placebo in a double-blind crossover study of 36 patients. The effect was evaluated using a 6-point verbal relief rating scale and by visual analog scale ratings of headache intensity before and for 2 h after treatment. Sumatriptan induced a modest but significantly greater headache relief than placebo, whereas no significant difference was found between the two doses of sumatriptan. Headache relief following sumatriptan was significant after 60 min and still seemed to be increasing after 120 min when the examination terminated. Three possible mechanisms of action of sumatriptan in tension-type headache are discussed.     

Drug‐induced aseptic meningitis: a mini‐review

Aseptic meningitis associates a typical clinical picture of meningitis with the absence of bacterial or fungal material in the cerebrospinal fluid. Drug‐induced aseptic meningitis (DIAM) may be due to two mechanisms: (i) a direct meningeal irritation caused by the intrathecal administration of drugs and (ii) an immunologic hypersensitivity reaction to a systemic administration. If the direct meningeal irritation allows a rather easy recognition, the immunologic hypersensitivity reaction is a source of challenging diagnostics. DIAM linked to a systemic treatment exerts typically an early onset, usually within a week. This period can be shortened to a few hours in case of drug rechallenge. The fast and spontaneous regression of clinical symptoms is usual after stopping the suspected drug. Apart from these chronological aspects, no specific clinical or biological parameters are pathognomonic. CSF analysis usually shows pleiocytosis. The proteinorachia is increased while glycorachia remains normal. Underlying pathologies can stimulate the occurrence of DIAM. Thus, systemic lupus erythematosus appears to promote DIAM during NSAID therapy, especially ibuprofen‐based one. Similarly, some patients with chronic migraine are prone to intravenous immunoglobulin‐induced aseptic meningitis. DIAM will be mainly evoked on chronological criteria such as rapid occurrence after initiation, rapid regression after discontinuation, and recurrence after rechallenge of the suspected drug. When occurring, positive rechallenge may be very useful in the absence of initial diagnosis. Finally, DIAM remains a diagnosis of elimination. It should be suggested only after all infectious causes have been ruled out.     

Headache Associated With Aseptic Meningitis

A retrospective analysis of all patients admitted with the diagnostic codes of aseptic or viral meningitis was performed at two institutions over 3 years. Forty-one patients with cerebrospinal fluid confirmation of aseptic meningitis (increased protein; increased white count; negative gram stain; and negative fungal, tuberculosis, and bacterial cultures) were analyzed.
All the patients had headache, which was typically severe and bilateral in 39 of the 41 patients. The headache was of abrupt onset or the worst of the patient's life in 24 of the patients. The quality of the headache, when described, was usually throbbing (11 of 14). Nineteen patients had prodromal symptoms, including malaise, myalgia, gastrointestinal symptoms, and urinary tract infections. All had associated symptoms, including nausea (25), vomiting (23), photophobia (18), stiff neck (25), and back pain (11). Thirty patients were febrile. Lumbar puncture was performed for headache and fever unexplained by systemic illness in 30 patients, meningeal signs in 15, headache of abrupt onset or the worst headache ever in 24, neurologic signs or symptoms in 12, and for other reasons in 2. Computerized tomography, when performed, was negative in all cases. Focal neurologic findings were present in 5 patients, a decreased level of consciousness in 6, and papilledema in 1.
A severe headache that worsens, is abrupt in onset, or is the worst of the patient's life could be due to aseptic meningitis, bacterial meningitis, or a subarachnoid hemorrhage. Although not universally present, meningeal signs, fever, and neurologic signs or symptoms should alert one to a possible central nervous system infection.     

无菌性脑膜炎暴发中病原学检测及埃柯30型肠道病毒的基因特征和分子进化分析

目的 了解引起福建省泉州地区2011年无菌性脑膜炎暴发疫情的埃柯30型肠道病毒(echovirus 30,ECHO30)病原及基因特征,分析基因变异情况及进化来源。 方法 对泉州市2011年无菌性脑膜炎暴发疫情中的临床样本采用实时荧光定量反转录-聚合酶链反应(rRT-PCR)方法进行肠道病毒通用型、肠道病毒71型(EV71)和柯萨奇病毒A组16型(Cox A16)核酸检测,随机选5份阳性样本进行肠道病毒VP1区核苷酸序列测定,将测序所得VP1序列用BLAST程序在GenBank上序列搜寻比对,确定其基因型, 并通过构建进化树分析其遗传进化规律。 结果 47份样本经rRT-PCR检测,有39份非EV71和Cox A16的其他肠道病毒核酸阳性, 5份阳性样本的肠道病毒VP1区核苷酸序列均为876 bp,且同源性最高,均大于98.9%,最高仅相差一个核苷酸,与它们具有较高同源性的均是ECHO30。与本次分离株亲缘关系最近的一组ECHO30分别是2008年河南省和浙江省的分离株,与中国台湾2001年无菌性脑炎分离株以及印度2011年分离株则距离较远;原型株Bastianni和20世纪90年代美国分离株和本次分离到的ECHO30毒株距离最远。 结论 2011年ECHO30在泉州地区发生一定程度的传播流行,并导致无菌性脑膜炎疫情的局部暴发流行,进化树分析表明本次分离株与国内近年ECHO30分离株亲缘关系较近,而与国外分离株则相对较远。     

Relationship between chronic tension-type headache, cranial hemodynamics, and cerebrospinal pressure: study involving provocation with sumatriptan

OBJECTIVE: To study the relationship between chronic tension-type headache, cranial hemodynamics, and cerebrospinal pressure. BACKGROUND: Cerebrospinal pressure has been found to be above 200 mm in about 50% of patients with chronic tension-type headache. METHODS: Heart rate, blood pressure, common carotid artery diameter and blood flow, and craniovascular resistance and pain at regular intervals before, during, and after head-down tilt-a procedure which increases cerebrospinal pressure, were recorded. After head-down tilt, subcutaneous injections of either placebo or 6 mg of sumatriptan were administered. Chronic tension-type headache intensity before and after withdrawal of 20 mL of cerebrospinal fluid was documented. Cerebrospinal pressure and chronic tension-type headache intensity were measured after subcutaneous injection of 6 mg of sumatriptan. RESULTS: Head-down tilt provoked an increase of headache compared with baseline. Common carotid artery blood flow decreased and craniovascular resistance increased after sumatriptan injection, but not after placebo injection. The pain decreased after head-down tilt and placebo injection, but not after sumatriptan injection. Chronic tension-type headache intensity decreased in all 4 patients studied after withdrawal of 20 mL of cerebrospinal fluid. Cerebrospinal pressure increased in 5 patients with chronic tension-type headache after subcutaneous injection of 6 mg of sumatriptan with slight or no increase of pain. CONCLUSION: The results indicated that cerebrospinal pressure or intracranial venous pressure (or both) are related to chronic tension-type headache.